Docetaxel-loaded solid lipid nanoparticles suppress breast cancer cells growth with reduced myelosuppression toxicity

Abstract

Docetaxel is an adjuvant chemotherapy drug widely used to treat multiple solid tumors; however, its toxicity and side effects limit its clinical efficacy. Herein, docetaxel-loaded solid lipid nanoparticles (DSNs) were developed to reduce systemic toxicity of docetaxel while still keeping its anticancer activity. To evaluate its anticancer activity and toxicity, and to understand the molecular mechanisms of DSNs, different cellular, molecular, and whole genome transcription analysis approaches were utilized. The DSNs showed lower cytotoxicity compared with the commercial formulation of docetaxel (Taxotere ® ) and induced more apoptosis at 24 hours after treatment in vitro. DSNs can cause the treated cancer cells to arrest in the G2/M phase in a dose-dependent manner similar to Taxotere. They can also suppress tumor growth very effectively in a mice model with human xenograft breast cancer. Systemic analysis of gene expression profiles by microarray and subsequent verification experiments suggested that both DSNs and Taxotere regulate gene expression and gene function, including DNA replication, DNA damage response, cell proliferation, apoptosis, and cell cycle regulation. Some of these genes expressed differentially at the protein level although their messenger RNA expression level was similar under Taxotere and DSN treatment. Moreover, DSNs improved the main side effect of Taxotere by greatly lowering myelosuppression toxicity to bone marrow cells from mice. Taken together, these results expound the antitumor efficacy and the potential working mechanisms of DSNs in its anticancer activity and toxicity, which provide a theoretical foundation to develop and apply a more efficient docetaxel formulation to treat cancer patients.

Possibilities in the application of solid lipid nanoparticles in combination with 5-fluorouracil to overcome the drugresistance of non-small cell lung cancer cell line A549

“…The increase in the apoptotic cell death in cancer cells is one of the most desirable effects of anti-tumour compounds due to the lack of inflammation induction by this type of death [23]. Moreover, addition of SNLs changed the cell cycle phase distribution especially in the case of SLNs modified with chitosan and cross-linked with 3 µM GA. Alterations in cell cycle after encapsulation of the drug in different types of nanoparticles including SLNs were also confirmed by available literature reports [24,25]. All of this suggests that the use of modified SLNs loaded with 5-FU may be beneficial in the treatment of 5-FU-resistant non-small cell lung cancer.…”

STAT3 Decoy Oligodeoxynucleotides-Loaded Solid Lipid Nanoparticles Induce Cell Death and Inhibit Invasion in Ovarian Cancer Cells

“…CTAB could facilitate gene loading and attachment between the nanoparticles and the cell surface. SLN have many advantages over other nanoformulations, such as easier preparation, safe component materials, low cost, better stability and controlled drug release [ 33 , 34 ].…”

Positive effects on hematological and biochemical imbalances in patients with metastatic breast cancer stage IV, of BP-C1, a new anticancer substance

“…These findings can be used to develop DSNs for human use. 20 Treatment of cancer patients with herbo-mineral and metallic Ayurvedic drugs has been reported to significantly reduce the toxic effects of chemotherapy on various symptoms, and to have improved QoL, 21 , 22 although no positive effects on hematological parameters could be demonstrated. Various herbal medicines have also been tested in cancer patients treated with chemotherapy, and these have been used to reduce chemotherapy-induced nausea and vomiting, to improve patients’ QoL and to allow their subsequent chemotherapy.…”